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Germano Guerra, Angela Lucariello, Angelica Perna, Laura Botta, Antonio De Luca, Francesco Moccia
BACKGROUND: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+ -dependent manner throughout peripheral vasculature...
March 21, 2018: International Journal of Molecular Sciences
Marwan Mannaa, Lajos Markó, András Balogh, Emilia Vigolo, Gabriele N'diaye, Mario Kaßmann, Laura Michalick, Ulrike Weichelt, Kai M Schmidt-Ott, Wolfgang B Liedtke, Yu Huang, Dominik N Müller, Wolfgang M Kuebler, Maik Gollasch
Transient receptor potential vanilloid 4 (TRPV4) cation channels are functional in all renal vascular segments and mediate endothelium-dependent vasorelaxation. Moreover, they are expressed in distinct parts of the tubular system and activated by cell swelling. Ischaemia/reperfusion injury (IRI) is characterized by tubular injury and endothelial dysfunction. Therefore, we hypothesised a putative organ protective role of TRPV4 in acute renal IRI. IRI was induced in TRPV4 deficient (Trpv4 KO) and wild-type (WT) control mice by clipping the left renal pedicle after right-sided nephrectomy...
March 20, 2018: Scientific Reports
Monika Lakk, Felix Vazquez-Chona, Oleg Yarishkin, David Križaj
Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell membranes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depletion or oversupply caused by diet or heredity contribute to neurodegenerative diseases and vision loss. Astroglia play a central role in the biosynthesis, uptake and transport of cholesterol and also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegenerative disease...
February 2018: Neural Regeneration Research
Viktor Tomilin, Gail A Reif, Oleg Zaika, Darren P Wallace, Oleh Pochynyuk
Autosomal-dominant polycystic kidney disease (ADPKD) is a devastating disorder that is characterized by a progressive decline in renal function as a result of the development of fluid-filled cysts. Defective flow-mediated [Ca2+ ]i responses and disrupted [Ca2+ ]i homeostasis have been repeatedly associated with cyst progression in ADPKD. We have previously demonstrated that the transient receptor potential vanilloid type 4 (TRPV4) channel is imperative for flow-mediated [Ca2+ ]i responses in murine distal renal tubule cells...
March 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
T Nodai, S Hitomi, K Ono, C Masaki, N Harano, A Morii, M Sago-Ito, I Ujihara, T Hibino, K Terawaki, Y Omiya, R Hosokawa, K Inenaga
Oral ulcer is the most common oral disease and leads to pain during meals and speaking, reducing the quality of life of patients. Recent evidence using animal models suggests that oral ulcers induce cyclooxygenase-dependent spontaneous pain and cyclooxygenase-independent mechanical allodynia. Endothelin-1 is upregulated in oral mucosal inflammation, although it has not been shown to induce pain in oral ulcers. In the present study, we investigated the involvement of endothelin-1 signaling with oral ulcer-induced pain using our proprietary assay system in conscious rats...
March 1, 2018: Journal of Dental Research
Marina M Bakri, Farhana Yahya, Khalil Munawar Makhdum Munawar, Junichi Kitagawa, Mohammad Zakir Hossain
OBJECTIVE: Transient receptor potential vanilloid 4 (TRPV4) has been considered as a mechano-, thermo- and osmo-receptor. Under inflammatory conditions in dental pulp, teeth can become sensitive upon exposure to a variety of innocuous stimuli. The objective of the present study was to investigate the expression of the TRPV4 channel on nerve fibers in human dental pulp of non-symptomatic and symptomatic teeth associated with inflammatory conditions. DESIGN: Dental pulp from extracted human permanent teeth was processed for fluorescence immunohistochemistry...
February 21, 2018: Archives of Oral Biology
Elizabeth L Evans, Kevin Cuthbertson, Naima Endesh, Baptiste Rode, Nicola M Blythe, Adam J Hyman, Sally J Hall, Hannah J Gaunt, Melanie J Ludlow, Richard Foster, David J Beech
BACKGROUND AND PURPOSE: The mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small-molecule agonist but the pharmacology of these channels is otherwise limited. EXPERIMENTAL APPROACH: Yoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in human umbilical vein endothelial cells (HUVECs) which natively express Piezo1...
March 2, 2018: British Journal of Pharmacology
Andrew J Shepherd, Aaron D Mickle, Suraj Kadunganattil, Hongzhen Hu, Durga P Mohapatra
Bone metastasis in breast, prostate and lung cancers often leads to chronic pain, which is poorly managed by existing analgesics. The neurobiological mechanisms that underlie chronic pain associated with bone-metastasized cancers are not well understood, but sensitization of peripheral nociceptors by tumor microenvironment factors has been demonstrated to be important. Parathyroid hormone-related peptide (PTHrP) is highly expressed in bone-metastasized breast and prostate cancers, and is critical to growth and proliferation of these tumors in the bone tumor microenvironment...
2018: Frontiers in Cellular Neuroscience
Michele A Corrigan, Gillian P Johnson, Elena Stavenschi, Mathieu Riffault, Marie-Noelle Labour, David A Hoey
Skeletal homeostasis requires the continued replenishment of the bone forming osteoblast from a mesenchymal stem cell (MSC) population, a process that has been shown to be mechanically regulated. However, the mechanisms by which a biophysical stimulus can induce a change in biochemical signaling, mechanotransduction, is poorly understood. As a precursor to loading-induced bone formation, deciphering the molecular mechanisms of MSC osteogenesis is a critical step in developing novel anabolic therapies. Therefore, in this study we characterize the expression of the mechanosensitive calcium channel Transient Receptor Potential subfamily V member 4 (TRPV4) in MSCs and demonstrate that TRPV4 localizes to areas of high strain, specifically the primary cilium...
February 28, 2018: Scientific Reports
Zengqin Deng, Navid Paknejad, Grigory Maksaev, Monica Sala-Rabanal, Colin G Nichols, Richard K Hite, Peng Yuan
The transient receptor potential (TRP) channel TRPV4 participates in multiple biological processes, and numerous TRPV4 mutations underlie several distinct and devastating diseases. Here we present the cryo-EM structure of Xenopus tropicalis TRPV4 at 3.8-Å resolution. The ion-conduction pore contains an intracellular gate formed by the inner helices, but lacks any extracellular gate in the selectivity filter, as observed in other TRPV channels. Anomalous X-ray diffraction analyses identify a single ion-binding site in the selectivity filter, thus explaining TRPV4 nonselectivity...
February 26, 2018: Nature Structural & Molecular Biology
Boris Martinac, Kate Poole
The ability of cells to sense and respond to their physical environment is fundamental to a broad spectrum of biological processes. Cells express an array of force sensors that can transduce mechanical inputs into biochemical signals, including the mechanically activated ion channels PIEZO1, PIEZO2 and TRPV4. The identification and characterisation of mechanically activated ion channels has proven challenging, as has identifying their mode of activation and regulation in vivo. However, the diverse channelopathies associated with the known channels highlights their physiological importance...
February 20, 2018: International Journal of Biochemistry & Cell Biology
Michael Camilleri
This is an editorial summarizing recent new developments in visceral analgesics. This promising field is important as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors through biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Jacquie Baker, Kurt Kimpinski
No abstract text is available yet for this article.
March 2018: Journal of Clinical Neuromuscular Disease
Sheng Cao, Andriy Anishkin, Natalya S Zinkevich, Yoshinori Nishijima, Ankush Korishettar, Zhihao Wang, Juan Fang, David A Wilcox, David X Zhang
TRPV4 is a Ca2+-permeable channel of the transient receptor potential (TRP) superfamily activated by diverse stimuli including warm temperature, mechanical forces, and lipid mediators such as arachidonic acid (AA) and its metabolites. This activation is tightly regulated by protein phosphorylation carried out by various serine/threonine or tyrosine kinases. It remains poorly understood how phosphorylation differentially regulates TRPV4 activation in response to different stimuli. We investigated how TRPV4 activation by AA, an important signaling process in the dilation of coronary arterioles, is affected by protein kinase A (PKA)-mediated phosphorylation at S824...
February 8, 2018: Journal of Biological Chemistry
William C Gordon, Virginia García López, Surjyadipta Bhattacharjee, David Rodríguez Gil, Javier Alcover Díaz, Fernando Pineda de la Losa, Ricardo Palacios Peláez, Concha Tiana Ferrer, Gabriela Silvina Bacchini, Bokkyoo Jun, Hélène Varoqui, Nicolas G Bazan
INTRODUCTION: A major clinical challenge in treating allergic contact dermatitis (ACD) is that the first line of treatment is based on the use of corticosteroids. In this study, we aimed to develop a formulation that is devoid of steroids. METHODS: We used mouse ears treated with dinitrofluorobenzene (DNFB) to induce ACD. The efficacy of the test formulation to ameliorate and to prevent induced ACD was determined. RESULTS: To treat this experimentally induced ACD, we developed a formulation containing BIPxine (a mixture of Rosa moschata and Croton lechleri (antioxidants) and Aloe vera and D-panthenol (moisturizers), and hydroglycolic solutions of disodium cromoglycate...
February 16, 2018: Dermatology and Therapy
Jin Yong An, Changhwan Ahn, Hee Young Kang, Eui-Bae Jeung
Calcium is important for physiological functioning in many tissues and is essential in mucus secretion and muscle contraction. Intracellular concentrations of calcium are regulated by calcium-related proteins such as TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1. In this study, the relationship between secretion of pulmonary mucus and calcium regulation was investigated. To confirm the effect of steroid hormones, immature mice were injected with estrogen (E2) or progesterone (P4) and mature mice were injected with dexamethasone (DEX)...
February 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Mengwen Qi, Chunfeng Wu, Zhouqing Wang, Li Zhou, Chen Men, Yimei Du, Songming Huang, Lei Chen, Ling Chen
BACKGROUND/AIMS: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs...
February 7, 2018: Cellular Physiology and Biochemistry
Mikie Hinata, Sunao Imai, Takao Sanaki, Junji Tsuchida, Takeshi Yoshioka, Kenichi Higashino, Miyuki Yamamoto, Masayuki Imai, Masahiko Soga, Narumi Horita, Isao Fukuda, Minoru Ikeda, Shoji Yamane, Atsushi Morita, Toshiyuki Kanemasa, Gaku Sakaguchi, Minoru Hasegawa, Masabumi Minami, Yasuhide Morioka
Transient receptor potential vanilloid 4 (TRPV4) receptor modulates pain, and this has been noted in several animal models. However, the involvement of TRPV4 in osteoarthritic (OA) pain remains poorly understood. The present study assessed the functional changes in TRPV4 and the expression of its endogenous ligand 5,6-epoxyeicosatrienoic acid (5,6-EET) in a rat monoiodoacetate (MIA)-induced OA pain model (MIA rats). MIA-treated rats showed reduced grip strength as compared with sham-treated rats, and this loss in function could be recovered by the intra-articular administration of a TRPV4 antagonist (HC067047 or GSK2193874)...
February 9, 2018: Pain
Marc-Henri Asmar, Louis Gaboury, Issam Saliba
Objectives Endolymphatic sac (ELS) pathophysiology in Ménière's disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: aquaporin-2 (AQP2), vasopressin receptor V2R, sodium potassium chloride cotransporter 2 (NKCC2), and transient receptor potential cation channel V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops...
February 1, 2018: Otolaryngology—Head and Neck Surgery
Lei Wen, Yue-Chun Wen, Gen-Jie Ke, Si-Qin Sun, Kai Dong, Lin Wang, Rong-Feng Liao
BACKGROUND: Ca2+ entry plays an important role in modulating endothelial cell migration and tube formation. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a Ca2+-permeable channel that is widely expressed in endothelial cells. It has been reported that TRPV4 is expressed in HRCECs and regulates Ca2+ entry. However, the function of TRPV4 in human retinal capillary endothelial cells (HRCECs) remains unknown. METHODS: In this study we used western blot and immunostaining assay to verify TRPV4 expression in HRCECs...
February 12, 2018: BMC Ophthalmology
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